Sildenafil is currently licensed for erectile dysfunction and not chronic use to treat central nervous system disorders there is evidence that it may play a neuroprotective effect in stroke. There have been reports that the lesions observed in multiple sclerosis (MS) patients may have an ischemic component, and therefore it is possible that chronic administration of sildenafil may be beneficial as a neuroprotective agent in clinical and experimental demyelinating diseases. To test this hypothesis, experimental allergic encephalomyeolitis (EAE) was induced by adoptive transfer of proteolipid protein sensitized Tcells in SJL mice. Mice were treated with either placebo vehicle or twice daily sildenafil 2mgkg commencing on day 10 after disease induction and followed for 120 days with 10 sildenafil treated and placebo mice euthanized every month for pathological analysis. The primary outcome measure was clinical score, with brain atrophy and neuropathological measures being secondary outcome measures. EAE Clinical scores showed that while sildenafil had no measurable effect on relapses compared to placebo treated animals however, sildenafil treated animals showed significantly less disease progression compared to placebo mice (p0.016). Neuropathological analysis demonstrated a significant reduction in Tcell count in treated mice. Placebo mice were additionally found to have a greater degree of brain atrophy compared to sildenafil treated mice. These results suggest that sildenafil may have an effect in EAE and further work is needed to evaluate the longterm effects in animals with established or other EAE disease models.